Journal article
ROR1 Potentiates FGFR Signaling in Basal-Like Breast Cancer
Cancers, Vol.11(5), p.718
05/01/2019
DOI: 10.3390/cancers11050718
PMCID: PMC6562526
PMID: 31137681
Abstract
Among all breast cancer types, basal-like breast cancer (BLBC) represents an aggressive subtype that lacks targeted therapy. We and others have found that receptor tyrosine kinase-like orphan receptor 1 (ROR1) is overexpressed in BLBC and other types of cancer and that ROR1 is significantly correlated with patient prognosis. In addition, using primary patient-derived xenografts (PDXs) and ROR1-knockout BLBC cells, we found that ROR1(+) cells form tumors in immunodeficient mice. We developed an anti-ROR1 immunotoxin and found that targeting ROR1 significantly kills ROR1(+) cancer cells and slows down tumor growth in ROR1(+) xenografts. Our bioinformatics analysis revealed that ROR1 expression is commonly associated with the activation of FGFR-mediated signaling pathway. Further biochemical analysis confirmed that ROR1 stabilized FGFR expression at the posttranslational level by preventing its degradation. CRISPR/Cas9-mediated ROR1 knockout significantly reduced cancer cell invasion at cellular levels by lowering FGFR protein and consequent inactivation of AKT. Our results identified a novel signaling regulation from ROR1 to FGFR and further confirm that ROR1 is a potential therapeutic target for ROR1(+) BLBC cells.
Details
- Title: Subtitle
- ROR1 Potentiates FGFR Signaling in Basal-Like Breast Cancer
- Creators
- Gaurav Pandey - University of IowaNicholas Borcherding - Medical Scientist Training Program, College of Medicine, University of Iowa, Iowa City, IA 52242, USA. nicholas-borcherding@uiowa.edu.Ryan Kolb - University of FloridaPaige Kluz - University of IowaWei Li - University of FloridaSonia Sugg - University of IowaJun Zhang - University of IowaDazhi A. Lai - SPEED BioSystems (United States)Weizhou Zhang - University of Florida
- Resource Type
- Journal article
- Publication Details
- Cancers, Vol.11(5), p.718
- DOI
- 10.3390/cancers11050718
- PMID
- 31137681
- PMCID
- PMC6562526
- NLM abbreviation
- Cancers (Basel)
- ISSN
- 2072-6694
- eISSN
- 2072-6694
- Publisher
- Mdpi
- Number of pages
- 16
- Grant note
- CA206255 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA CA200673; CA203834 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA T32GM007337 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) BC180227 / DOD Congressionally Directed Medical Research Programs (CDMRP) R01CA203834; P30CA086862; F30CA206255; R01CA200673 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 05/01/2019
- Academic Unit
- Dermatology; Orthopedics and Rehabilitation; Surgery; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984322806002771
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